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The spectrin membrane skeleton controls the disposition of selected membrane channels, receptors, and transporters. In the brain βIll spectrin binds directly to the excitatory amino acid transporter (EAAT4), the glutamate receptor delta, and other proteins. Mutations in βlll spectrin link strongly to human spinocerebellar ataxia type 5 (SCA5), correlating with alterations in EAAT4. We have explored the mechanistic basis of this phenotype by targeted gene disruption of Spnb3; Mice lacking intact βlll spectrin develop normally. By 6 months they display a mild nonprogressive ataxia. By 1 year most Spnb3-/- animals develop a myoclonic seizure disorder with significant reductions of EAAT4, EAAT1,. GluRδ, IP3R, and NCAM140. Other synaptic proteins are normal. The cerebellum displays increased dark Purkinje cells (PC), a thin molecular layer, fewer synapses, a loss of dendritic spines, and a 2-fold expansion of the PC dendrite diameter. Membrane and expanded Golgi profiles fill the PC dendrite and soma, and both regions accumulate EAAT4. Correlating with the seizure disorder are enhanced hippocampal levels of neuropeptide V and EAAT3 and increased calpain proteolysis of all spectrin. It appears that δlll spectrin disruption impairs synaptogenesis by disturbing the intracellular pathways selectively regulating protein trafficking to the synapse. The mislocalization of these proteins secondarily disrupts glutamate transport dynamics, leading to seizures, neuronal damage, and compensatory changes in EAAT3 and neuropeptide Y. [ABSTRACT FROM AUTHOR]

Background Context: A deep learning (DL) model for degenerative cervical spondylosis on MRI could enhance reporting consistency and efficiency, addressing a significant global health issue., Purpose: Create a DL model to detect and classify cervical cord signal abnormalities, spinal canal and neural foraminal stenosis., Study Design/setting: Retrospective study conducted from January 2013 to July 2021, excluding cases with instrumentation., Patient Sample: Overall, 504 MRI cervical spines were analyzed (504 patients, mean=58 years±13.7[SD]; 202 women) with 454 for training (90%) and 50 (10%) for internal testing. In addition, 100 MRI cervical spines were available for external testing (100 patients, mean=60 years±13.0[SD];26 women)., Outcome Measures: Automated detection and classification of spinal canal stenosis, neural foraminal stenosis, and cord signal abnormality using the DL model. Recall(%), inter-rater agreement (Gwet's kappa), sensitivity, and specificity were calculated., Methods: Utilizing axial T2-weighted gradient echo and sagittal T2-weighted images, a transformer-based DL model was trained on data labeled by an experienced musculoskeletal radiologist (12 years of experience). Internal testing involved data labeled in consensus by 2 musculoskeletal radiologists (reference standard, both with 12-years-experience), 2 subspecialist radiologists, and 2 in-training radiologists. External testing was performed., Results: The DL model exhibited substantial agreement surpassing all readers in all classes for spinal canal (κ=0.78, p<.001 vs κ range=0.57-0.70 for readers) and neural foraminal stenosis (κ=0.80, p<.001 vs κ range=0.63-0.69 for readers) classification. The DL model's recall for cord signal abnormality (92.3%) was similar to all readers (range: 92.3-100.0%). Nearly perfect agreement was demonstrated for binary classification (grades 0/1 vs 2/3) (κ=0.95, p<.001 for spinal canal; κ=0.90, p<.001 for neural foramina). External testing showed substantial agreement using all classes (κ=0.76, p<.001 for spinal canal; κ=0.66, p<.001 for neural foramina) and high recall for cord signal abnormality (91.9%). The DL model demonstrated high sensitivities (range:83.7%-92.4%) and specificities (range:87.8%-98.3%) on both internal and external datasets for spinal canal and neural foramina classification., Conclusions: Our DL model for degenerative cervical spondylosis on MRI showed good performance, demonstrating substantial agreement with the reference standard. This tool could assist radiologists in improving the efficiency and consistency of MRI cervical spondylosis assessments in clinical practice., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Cauda Equina Syndrome (CES) poses significant neurological risks if untreated. Diagnosis relies on clinical and radiological features. As the symptoms are often non specific and common, the diagnosis is usually made after a MRI scan. A huge number of MRI scans are done to exclude CES but nearly 80% of them will not have cauda equina syndrome. This study aimed to develop and validate a machine learning model for automated CES detection from MRI scans to enable faster triage of patients presenting with CES like clinical features., Methods: MRI scans from suspected CES patients (2017-2022) were collected and categorized into normal scans/disc protrusion (0%-50% canal stenosis (CS)) and cauda equina compression (CEC, >50% CS). A convolutional neural network was developed and tested on a total of 715 images (80:20 split) Gradient descent heatmaps were generated to highlight regions crucial for classification., Results: The model achieved an accuracy of 0.950 (0.921-0.971), a sensitivity of 0.969 (0.941-0.987), a specificity of 0.859 (0.742-0.937), a positive predictive value of 0.969 (0.944-0.984) and an area under the curve of 0.915 (0.865-0.958). Gradient descent heatmaps demonstrated accurate identification of any clinically relevant disc herniation into the spinal canal., Conclusions: This study pilots a deep learning approach for predicting CEC presence, promising improved healthcare quality and timely CES management. As referrals rise, this tool can act as a fast triage system which can lead to prompt management of CES in environments where resources for radiological interpretation of mri scans is limited., (Copyright © 2025. Published by Elsevier Inc.)

There are various models for acute neurology services in the UK, with considerable variation in practice. Patients are often admitted unnecessarily for neurology review, leading to delay in diagnosis and treatment. Alternative models, such as the Neurology Same Day Emergency Care service (Neuro-SDEC) at University College London Hospital provide a pathway that can prevent admissions and streamline patient care. Headache is one of the commonest presenting symptoms in acute neurology.This study compared the impact of Neuro-SDEC on the care for patients presenting with headache against the standard pathway.A prospective audit was undertaken from November - December 2023 to evaluate all appropriate patients seen by the Neuro-SDEC service or admitted to the ward. For Neuro-SDEC patients, each case was reviewed to see whether an admission, lumbar puncture or neurology outpatient referral was avoided. For admitted patients, length of inpatient stay, time to neurology review and discharge diagnosis was recorded.Fifty-one patients were seen by Neuro-SDEC, twenty-five of whom would have been admitted to hospital on the standard pathway. Thirty general neurology outpatient clinic referrals were prevented and 5 patients avoided a lumbar puncture. In 45% of cases, the working diagnosis changed after the patient was seen by the Neuro-SDEC team. There were seven admitted patients not seen by the service with a combined length of stay of 17 bed days. The average wait time for inpatient neurology review was 42 hours. 3 admitted patients underwent a lumbar puncture. 2 patients were referred on to neuro-SDEC to enable an earlier discharge from hospital. Migraine was the most common final diagnosis in both groups.This study highlights that Neuro-SDEC is effective at reducing hospital admissions, as well as unnecessary tests and referrals to generalneurology outpatients. For admitted patients, the service enabled earlier discharge from hospital and reduced length of stay., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Foams are versatile by nature and ubiquitous in a wide range of applications, including padding, insulation, and acoustic dampening. Previous work established that foams 3D printed via Viscous Thread Printing (VTP) can in principle combine the flexibility of 3D printing with the mechanical properties of conventional foams. However, the generality of prior work is limited due to the lack of predictable process-property relationships. In this work, a self-driving lab is utilized that combines automated experimentation with machine learning to identify a processing subspace in which dimensionally consistent materials are produced using VTP with spatially programmable mechanical properties. In carrying out this process, an underlying self-stabilizing characteristic of VTP layer thickness is discovered as an important feature for its extension to new materials and systems. Several complex exemplars are constructed to illustrate the newly enabled capabilities of foams produced via VTP, including 1D gradient rectangular slabs, 2D localized stiffness zones on an insole orthotic and living hinges, and programmed 3D deformation via a cable-driven humanoid hand. Predictive mapping models are developed and validated for both thermoplastic polyurethane (TPU) and polylactic acid (PLA) filaments, suggesting the ability to train a model for any material suitable for material extrusion (ME) 3D printing., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Most neurons are not replaced after injury and thus possess robust intrinsic mechanisms for repair after damage. Axon injury triggers a calcium wave, and calcium and cAMP can augment axon regeneration. In comparison to axon regeneration, dendrite regeneration is poorly understood. To test whether calcium and cAMP might also be involved in dendrite injury signaling, we tracked the responses of Drosophila dendritic arborization neurons to laser severing of axons and dendrites. We found that calcium and subsequently cAMP accumulate in the cell body after both dendrite and axon injury. Two voltage-gated calcium channels (VGCCs), L-Type and T-Type, are required for the calcium influx in response to dendrite injury and play a role in rapid initiation of dendrite regeneration. The AC8 family adenylyl cyclase, Ac78C, is required for cAMP production after dendrite injury and timely initiation of regeneration. Injury-induced cAMP production is sensitive to VGCC reduction, placing calcium upstream of cAMP generation. We propose that two VGCCs initiate global calcium influx in response to dendrite injury followed by production of cAMP by Ac78C. This signaling pathway promotes timely initiation of dendrite regrowth several hours after dendrite damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hertzler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Early diagnosis, intervention, and therapeutic advancements have extended the lives of breast cancer patients; however, even with molecularly targeted therapies, many patients eventually progress to metastatic cancer. Recent data suggest that residual breast cancer cells often reside in the lymphatic system before rapidly spreading through the bloodstream. To address this challenge, an effective drug combination composed of gemcitabine (G) and paclitaxel (T) is administered intravenously in sequence at the metastatic stage, but intravenous GT infusion may limit lymphatic GT drug accessibility and asynchronous drug exposure in cancer cells within the lymph. To determine whether co-localization of intracellular gemcitabine and paclitaxel (referred to as GT) could overcome these limitations and enhance the efficacy of GT, we have evaluated a previously reported GT drug-combination formulated in nanoparticle (referred to as GT-in-DcNP) evaluated in an orthotopic breast tumor model. Previously, with indocyanine green-labeled nanoparticles, we reported that GT-in-DcNP particles after subcutaneous dosing were taken up rapidly and preferentially into the lymph instead of blood vessels. The pharmacokinetic study showed enhanced co-localization of GT within the tumors and likely through lymphatic access, before drug apparency in the plasma leading to apparent long-acting plasma time-course. The mechanisms may be related to significantly greater inhibitions of tumor growth-by 100 to 140 times-in both sub-iliac and axillary regions compared to the equivalent dosing with free-and-soluble GT formulation. Furthermore, GT-in-DcNP exhibited dose-dependent effects with significant tumor regression. In contrast, even at the highest dose of free GT combination, only a modest tumor growth reduction was notable. Preliminary studies with MDA-231-HM human breast cancer in an orthotopic xenograft model indicated that GT-in-DcNP may be effective in suppressing human breast tumor growth. Taken together, the synchronized delivery of GT-in-DcNP to mammary tumors through the lymphatic system offers enhanced cellular retention and greater efficacy.

The common bean (Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture., (© 2024. The Author(s).)

Loss-of-function (LoF) mutations in the filaggrin gene (FLG) constitute the strongest genetic risk for atopic dermatitis (AD). A latitude-dependent difference in the prevalence of LoF FLG mutations was systematically evaluated. A systematic review and meta-analysis were performed to estimate the prevalence of LoF FLG mutations in AD patients and the general population by geography and ethnicity. Risk of bias was assessed by Newcastle-Ottawa Scale and Jadad score. StatsDirect, version 3 software was used to calculate all outcomes. PubMed and EMBASE were searched until 9 th  December 2021. Studies were included if they contained data on the prevalence of LoF FLG mutations in AD patients or from the general population or associations between AD and LoF FLG mutations and were authored in English. Overall, 248 studies and 229 310 AD patients and individuals of the general population were included in the quantitative analysis. The prevalence of LoF FLG mutations was 19.1% (95% CI, 17.3-21.0) in AD patients and 5.8% (95% CI, 5.3-6.2) in the general population. There was a significant positive association between AD and LoF FLG mutations in all latitudes in the Northern hemisphere, but not in all ethnicities. The prevalence of LoF FLG mutations became gradually more prevalent in populations residing farther north of the Equator but was negligible in Middle Easterners and absent in most African populations. FLG LoF mutations are common and tend to increase with northern latitude, suggesting potential clinical implications for future AD management. The existence of possible genetic fitness from FLG LoF mutations remains unknown., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Femoral neck fractures (FNF) are one of the most common fractures, with a projected increase in incidence with population growth and ageing. The Femoral Neck System (FNS) launched in 2019 was developed specifically for fixation of FNF with the purported advantages of providing both angular and rotational stability. We report our experience with the FNS and evaluate its effectiveness and associated complications., Methods: A retrospective case series of 50 patients who underwent surgical fixation for FNF from August 2020 to October 2021 using the FNS in two Singapore tertiary institutions with at least 2 years follow-up were included. Clinical data (patients' demographics, fracture classification, intra-operative and post-operative complications) were reviewed. Radiological analysis assessed the pre- and immediate post-operative garden alignment index (GAI) and presence of femoral neck shortening at 3 months., Results: The mean age was 63.5 years (SD 16.9, range 26-92). Five (10 %), 34 (68 %) and 11 (22 %) were ASA 1, 2 and 3 respectively. Twenty-four (48 %), 16 (32 %), 4 (8 %), and 6 (12 %) patients sustained Garden's 1, 2, 3 and 4 FNF respectively. The mean operative duration was 66.2 min (SD 20.5) and length of stay was 6.9 days (SD 4.6).The post-operative improvement in garden alignment index (GAI) was a mean of 9.1° (p < 0.001) on lateral view. The mean femoral neck shortening was 1.97 mm (SD 5.3) at 3 months. There were no intra-operative complications. Post-operatively, 1 (2 %) patient required blood transfusion, 1 (2 %) patient had implant cut-out and non-union managed non-operatively, 2 (4 %) patients developed avascular necrosis and required revision to total hip replacements. There were two (4 %) cases of 1-year mortality., Conclusion: The FNS achieved good outcomes with low rates of complications. The promising results justify its continued use and further evaluation in comparison to other devices., Competing Interests: The authors have no conflicts of interest to declare. (Unable to edit and save the Conflict of Interest Form provided in the link in the portal), (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Pediatric foreign bodies (FBs) come in many shapes and sizes, and the method by which they enter the body can greatly impact the level of acuity at presentation. Most FBs in children are found in those younger than 5 years old, but the following 3 cases were found in adolescent patients., Case Presentation: We report on 3 adolescent patients who presented to a single community-based emergency department with the chief complaint of abdominal pain and were found to have complications of abdominal FBs. If undiagnosed, the initial indolent courses of FBs can lead to serious complications, as shown in these examples., Conclusion: These cases emphasize the need for physicians to maintain a high level of suspicion, to perform detailed histories, and to consider advanced imaging despite reassuring vital signs or physical examination., Competing Interests: Conflicts of Interest The authors declare they have no conflicts of interest., (© 2023 HCA Physician Services, Inc. d/b/a Emerald Medical Education.)

We determined which educational and/or psychological interventions were most effective in atopic dermatitis (AD). A systematic review of published studies evaluated the effectiveness of educational and/or psychological interventions in MEDLINE, Embase, SCOPUS, LILACS, Cochrane, China National Knowledge Infrastructure, Taiwan Electronic Periodical Services, and CiNii. Two reviewers conducted title/abstract, full-text review, and data extraction. Twenty-four prospective studies were included, including 20 randomized controlled trials. Educational (4/7 studies) and combined educational and psychological (5/6 studies) interventions reduced AD severity; psychological (10/11 studies) interventions showed the greatest benefit. The most commonly studied psychological intervention was habit reversal training (8/11 studies), which was most frequently incorporated in studies that reduced AD severity (8/10 studies). The most commonly studied educational interventions were education on AD triggers (7/7 studies) and skin care (7/7 studies); they were incorporated in all studies that reduced AD severity. Different psychological and/or educational interventions successfully reduced AD severity, especially habit reversal training.

To alleviate the energy and environmental crisis, in the last decades, energy harvesting by utilizing optical control has emerged as a promising solution. Here we report a polar crystal that exhibits photoenergy conversion and energy storage upon light irradiation. The polar crystal consists of dinuclear [CoGa] molecules, which are oriented in a uniform direction inside the crystal lattice. Irradiation with green light induces a directional intramolecular electron transfer from the ligand to a low-spin Co III centre, and the resultant light-induced high-spin Co II excited state is trapped at low temperature, realizing energy storage. Additionally, electric current release is observed during relaxation from the trapped light-induced metastable state to the ground state, because the intramolecular electron transfer in the relaxation process is accompanied with macroscopic polarization switching at the single-crystal level. It demonstrates that energy storage and conversion to electrical energy is realized in the [CoGa] crystals, which is different from typical polar pyroelectric compounds that exhibit the conversion of thermal energy into electricity., (© 2023. The Author(s).)

Background: Cobalt is a recognized cause of allergic contact dermatitis (ACD); however, detailed information on patient characteristics, sites, and sources is lacking. Objective: The aim of the study is to assess trends in patch test reactions to cobalt and associated patient characteristics, common sources, and body sites affected. Methods: The study used a retrospective analysis of adult patients who were patch tested to cobalt by the North American Contact Dermatitis Group between 2001 and 2018 (n = 41,730). Results: Overall, 2986 (7.2%) and 1362 (3.3%) had allergic or currently relevant patch test reaction to cobalt, respectively. Patients with versus without an allergic patch test reaction to cobalt were more likely to be female, employed, have a history of eczema or asthma, be Black, Hispanic, or Asian, and have occupational-related dermatitis. The most commonly identified sources of cobalt in allergic patients included jewelry, belts, and cement, concrete, and mortar. Affected body site(s) varied by cobalt source among patients with currently relevant reactions. Occupational relevance was found in 16.9% of patients with positive reactions. Conclusions: Positive patch test reactions to cobalt were common. The most common body sites were the hands, and affected site varied by the source of cobalt.

Unlike many cell types, neurons are not typically replaced if damaged. Therefore, regeneration of damaged cellular domains is critical for maintenance of neuronal function. While axon regeneration has been documented for several hundred years, it has only recently become possible to determine whether neurons respond to dendrite removal with regeneration. Regrowth of dendrite arbors has been documented in invertebrate and vertebrate model systems, but whether it leads to functional restoration of a circuit remains unknown. To test whether dendrite regeneration restores function, we used larval Drosophila nociceptive neurons. Their dendrites detect noxious stimuli to initiate escape behavior. Previous studies of Drosophila sensory neurons have shown that dendrites of single neurons regrow after laser severing. We removed dendrites from 16 neurons per animal to clear most of the dorsal surface of nociceptive innervation. As expected, this reduced aversive responses to noxious touch. Surprisingly, behavior was completely restored 24 ​h after injury, at the stage when dendrite regeneration has begun, but the new arbor has only covered a small portion of its former territory. This behavioral recovery required regenerative outgrowth as it was eliminated in a genetic background in which new growth is blocked. We conclude that dendrite regeneration can restore behavior., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions)., Methods and Analysis: Pregnant women aged 15-49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses., Ethics and Dissemination: Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: OSPREY personal armour has been issued to UK forces since 2005. From 2015, the VIRTUS personal armour and load carriage system have been progressively replacing OSPREY. In 2016, the ban on women in ground close combat roles throughout the UK's Armed Forces was lifted. In anticipation of this, work has been ongoing to prepare future ballistic protection programmes for a potential increase in the number of female users., Method: A human factors questionnaire was provided to 150 female users of OSPREY body armour to complete while on combat operations in Afghanistan. The questionnaire asked the users to rate the comfort of their OSPREY body armour along with their ability to carry out basic tasks. Other background data such as size of body armour worn and bra size were also collected for the analysis., Results: The female participants reported various types of discomfort when wearing their OSPREY body armour, with 135 instances of discomfort experienced in the hip region, for example. Challenges were reported in the ability to carry out basic movements, with the tasks rated on a Likert scale as difficult or very difficult by between 29% and 59% of participants. In addition, a restriction in ability to access personal equipment worn on the person (including pouches, trouser pockets) was commented on by 39% of participants., Conclusions: Female users reported challenges relating to the fit and function of OSPREY body armour. The VIRTUS body armour system for UK Armed Forces Personnel has already addressed many of the reported issues with OSPREY. Further optimisation for VIRTUS with regard to female users is planned and includes sizing of ballistic hard plates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic subdural hematoma (CSDH) incidence and referral rates to neurosurgery are increasing. Accurate and automated evidence-based referral decision-support tools that can triage referrals are required. Our objective was to explore the feasibility of machine learning (ML) algorithms in predicting the outcome of a CSDH referral made to neurosurgery and to examine their reliability on external validation., Methods: Multicenter retrospective case series conducted from 2015 to 2020, analyzing all CSDH patient referrals at two neurosurgical centers in the United Kingdom. 10 independent predictor variables were analyzed to predict the binary outcome of either accepting (for surgical treatment) or rejecting the CSDH referral with the aim of conservative management. 5 ML algorithms were developed and externally tested to determine the most reliable model for deployment., Results: 1500 referrals in the internal cohort were analyzed, with 70% being rejected referrals. On a holdout set of 450 patients, the artificial neural network demonstrated an accuracy of 96.222% (94.444-97.778), an area under the receiver operating curve (AUC) of 0.951 (0.927-0.973) and a brier score loss of 0.037 (0.022-0.056). On a 1713 external validation patient cohort, the model demonstrated an AUC of 0.896 (0.878-0.912) and an accuracy of 92.294% (90.952-93.520). This model is publicly deployed: https://medmlanalytics.com/neural-analysis-model/., Conclusion: ML models can accurately predict referral outcomes and can potentially be used in clinical practice as CSDH referral decision making support tools. The growing demand in healthcare, combined with increasing digitization of health records raises the opportunity for ML algorithms to be used for decision making in complex clinical scenarios., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)

Background: Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients. Methods: A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits. Results: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20]). Conclusions: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course.

The exocyst complex is an important regulator of intracellular trafficking and tethers secretory vesicles to the plasma membrane. Understanding of its role in neuron outgrowth remains incomplete, and previous studies have come to different conclusions about its importance for axon and dendrite growth, particularly in vivo. To investigate exocyst function in vivo we used Drosophila sensory neurons as a model system. To bypass early developmental requirements in other cell types, we used neuron-specific RNAi to target seven exocyst subunits. Initial neuronal development proceeded normally in these backgrounds, however, we considered this could be due to residual exocyst function. To probe neuronal growth capacity at later times after RNAi initiation, we used laser microsurgery to remove axons or dendrites and prompt regrowth. Exocyst subunit RNAi reduced axon regeneration, although new axons could be specified. In control neurons, a vesicle trafficking marker often concentrated in the new axon, but this pattern was disrupted in Sec6 RNAi neurons. Dendrite regeneration was also severely reduced by exocyst RNAi, even though the trafficking marker did not accumulate in a strongly polarized manner during normal dendrite regeneration. The requirement for the exocyst was not limited to injury contexts as exocyst subunit RNAi eliminated dendrite regrowth after developmental pruning. We conclude that the exocyst is required for injury-induced and developmental neurite outgrowth, but that residual protein function can easily mask this requirement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Asbestos mining operations have left South Africa with a legacy of asbestos contamination and asbestos-related diseases continue to be a problem. The large-scale mining of three types of asbestos presents a unique opportunity to study malignant mesothelioma of the pleura (mesothelioma) in South Africa. This study aimed to describe the demographics of deceased individuals diagnosed with mesothelioma and explore any associations between the histological morphology of mesothelioma and asbestos characteristics. We reviewed the records of all deceased miners and ex-miners from the Pathology Automation System (PATHAUT) database of the National Institute of Occupational Health (NIOH) that were histologically diagnosed with mesothelioma in the period from January 2006-December 2016 (11 years). The study population does not include all cases of mesothelioma in South Africa but rather those that reached the compensation system. Crocidolite asbestos fibres were identified in the majority of mesothelioma cases ( n = 140; 53.4%). The epithelioid subtype was most commonly present in both occupational and environmental cases. Cases with the sarcomatous subtype were older at death and fewer female cases were diagnosed with this subtype. No relationship between mesothelioma subtype and asbestos type or asbestos burden or fibre size was established.

Background: The relationship between atopic dermatitis (AD) severity, sleep disturbance (SD), and health-related outcomes is not fully elucidated., Objective: The aim of the study was to determine the prevalence of SD in adult AD and its relationship with AD severity and health outcomes among the US population., Methods: A cross-sectional, US population-based survey study of 2893 adults was performed., Results: Among adults meeting the UK Diagnostic Criteria for AD, 255 (40.7%) reported 1 or more, 67 (11.1%) reported 3 to 4, and 57 (9.5%) reported 5 to 7 nights of SD in the past week; 475 (79.7%) reported at least some trouble sleeping in the past 3 days. Moderate and severe Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, and Numeric Rating Scale-itch and Numeric Rating Scale-skin pain scores were associated with more severe SD compared with those without AD. More frequent and severe SDs were associated with higher Dermatology Life Quality Index, lower 12-item Short-Form Health Survey, and higher Hospital Anxiety and Depression Scale (HADS) scores. Significant mediation by SD severity was observed between Patient-Oriented Eczema Measure and Numeric Rating Scale-itch with Dermatology Life Quality Index, 12-item Short-Form Health Survey physical and mental component scores, HADS-anxiety and HADS-depression scores, diagnosed anxiety, and heart disease., Conclusions: Atopic dermatitis and AD severity are associated with SDs. Sleep disturbances considerably impact quality of life and other health outcomes in adults with AD., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Obesity is associated with reduced mortality in some patients hospitalized for heart failure (HF). In this analysis, we determine if this nonlinear relation, referred to as the obesity paradox, extends to secondary outcomes in patients diagnosed with severe obesity. This is a retrospective cohort study using the 2017 and 2018 National Inpatient Sample that includes adults hospitalized for HF. Patients with diagnosis codes specifying severe obesity, nonsevere obesity, or without obesity are compared. The primary outcome is mortality. Secondary outcomes include the length of stay (LOS), total charges, and cardiogenic shock (CS). Multivariate regression is used to adjust for demographics and co-morbidities. A total of 2,439,845 hospitalizations are included. A decreased mortality is found in nonsevere obesity (odds ratio 0.74, 95% confidence interval 0.69 to 0.80, p = 0.000), affirming the obesity paradox. However, this decreased mortality is not found in severe obesity (odds ratio 1.01, 95% confidence interval 0.94 to 1.08, p = 0.766). Severe obesity and nonsevere obesity are also associated with less CS and increased LOS compared with non-obese patients. Severe obesity is associated with increased total charges. In conclusion, a nonlinear, U-shaped relation between obesity and mortality in patients hospitalized for HF is demonstrated, where those not obese and those severely obese experience greater mortality compared with the nonseverely obese. However, for secondary outcomes of CS, LOS, and total charges, the relation is linear and therefore not interpreted as paradoxical. More information is needed using the adiposity-based chronic disease model to characterize complex relations between obesity and mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Prolonged uncontrolled hyperglycaemia has shown to cause oxidative stress, inflammation, thrombosis and upregulation of angiogenesis in diabetics, which all contributes to diabetic retinopathy development and progression. Vitamin E is found to have anti-inflammatory, anti-oxidative, anti-thrombogenic and anti-angiogenesis which could play an important role in early treatment of diabetic retinopathy. This study aims to investigate the effect of Tocotrienol-rich vitamin E (Tocovid) on the progression of retinal microhaemorrhages and diabetic macular oedema in patients with diabetic retinopathy., Method: This is a multi-centred, randomized, double-blinded, placebo-controlled trial which involved 55 eligible participants. The participants in the treatment group ( n  = 22) received Tocovid 200 mg twice daily while those in the placebo group ( n  = 23) would receive placebo twice daily. Both groups will be on the treatment for a total duration of 12 months. Both retinal signs will be assessed at baseline, 2 months, 6 months and 12 months of treatment to determine the progression of diabetic retinopathy. Serum vascular endothelial growth factor which reflects on the angiogenesis process in the eye was analysed as well at similar time points as the retinal findings., Results: After 12 months of treatment, the placebo group had a significant increase of 23.42% in retinal microhaemorrhages ( p  < 0.05), but the Tocovid group had no significant changes. Moreover, the Tocovid group showed a significant decrease of 48.38% in area of diabetic macular oedema over the 12 months period ( p  < 0.05), but the placebo group had no significant changes. Meanwhile, there was no significant difference in serum vascular endothelial growth factor level when comparing between both groups., Conclusion: These findings could indicate that Tocovid has an important role in preventing early diabetic retinopathy progression., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2022.)

Objectives: The aim of this study was to investigate whether the addition of intravascular ultrasound (IVUS) guidance during femoropopliteal artery interventions reduced the rate of binary restenosis within 12 months compared with angiographic guidance alone., Background: IVUS is more accurate than angiography for assessment of vessel size and disease severity. Low-level studies suggest that the use of IVUS in femoropopliteal endovascular interventions improves outcomes, but currently, no level 1 evidence exists., Methods: This was a prospective single-center trial of 150 patients undergoing femoropopliteal endovascular intervention, randomized (1:1) to guidance by angiography or angiography and IVUS. The primary outcome measure was freedom from binary restenosis, on duplex ultrasound, within 12 months. Secondary outcomes included clinically driven target lesion revascularization, disagreements in imaging findings between modalities, and changes in treatment caused by IVUS., Results: Freedom from binary restenosis at 12 months was significantly higher in the IVUS group (72.4% vs 55.4%; P = 0.008). There was no significant difference between groups for clinically directed target lesion revascularization (84.2% and 82.4%; P = 0.776). Mean vessel diameter was significantly larger with IVUS (5.60 mm vs 5.10 mm; P < 0.001). A change in treatment occurred caused by IVUS in 79% of cases. Binary restenosis was lower in the IVUS group for cases treated with drug-coated balloons (9.1% vs 37.5%; P = 0.001)., Conclusions: The use of IVUS resulted in a significant reduction in the rate of restenosis after endovascular intervention. This is the first randomized controlled trial to demonstrate that IVUS improves outcomes in femoropopliteal interventions. This benefit may primarily relate to cases treated with drug-coated balloons. (Does the use of intravascular ultrasound improve outcomes of endovascular interventional procedures for peripheral vascular disease of the superficial femoral artery or popliteal artery?; ACTRN12614000006640)., Competing Interests: Funding Support and Author Disclosures Dr Allan was the recipient of Health Professional Scholarship No. 100668 from the National Heart Foundation of Australia in the duration of this study. The National Heart Foundation of Australia had no involvement in the study design or collection, analysis, and interpretation of data. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sleep disturbance (SD) is common in atopic dermatitis (AD). We examined the longitudinal course of SD and relationship with itch in AD patients., Methods: A prospective, dermatology practice-based study was performed (N = 1295) where patients were assessed at baseline and follow-up visits., Results: At baseline, 16.9% of the patients had severe SD based on Patient-Reported Outcomes Information System (PROMIS) SD T scores, 19.1% had difficulty falling asleep, 22.9% had difficulty staying asleep, and 34.2% had SD from AD. A total of 31.4% of the patients with difficulty staying asleep at baseline experienced persistent difficulties (for 3 follow-ups or more). Only 17.7% with baseline difficulty falling asleep had persistent disturbance. Despite significant fluctuation in sleep scores, SD generally improved over time. Of the patients facing baseline SD from AD, 31.5% experienced SD at the first visit, and only 12.3% experienced persistent SD at the second follow-up visit. Predictors of increased PROMIS sleep-related impairment T scores over time included baseline PROMIS sleep-related impairment T scores (0.74 [0.68-0.80]), having 3 to 6 nights of itch (2.22 [0.85-3.59]), and severe/very severe AD (4.40 [2.60-6.20])., Conclusions: A significant proportion of adult AD patients, particularly those with moderate-severe AD and frequent itch, had baseline SD. Although sleep scores generally improved over time, many patients experienced a fluctuating or persistent course., Competing Interests: R.C. and S.G. are employees of Galderma. J.I.S. has been a consultant for Galderma. No other authors have any conflicts of interest to declare., (Copyright © 2022 American Contact Dermatitis Society.)

Purpose: The ideal method of central slip reconstruction is difficult to determine due to the multitude of techniques, nonstandardized outcome reporting, and small patient series in the literature. Although most boutonniere deformities may be treated with nonsurgical measures, chronic, subacute, or open injuries may require operative intervention. To aid surgeons in the choice of the ideal central slip reconstruction method, this biomechanical study compared the 3 most common methods performed at our institution: direct repair, lateral band centralization, and distally-based flexor digitorum superficialis (FDS) slip repair., Methods: A boutonniere deformity was induced in 35 fresh-frozen cadaver digits. The central slip was repaired in 9 digits using a primary suture repair, in 9 digits using a lateral band centralization technique, and in 9 digits using a distally-based FDS slip reconstruction. A control group without injury was tested in 8 digits. Following repair or reconstruction, each digit was tested for load to failure, strain, and stiffness at the repair., Results: The average load to failure after central slip reconstruction was significantly greater for a distally based FDS slip method at 82.1 ± 14.6 N (95% CI, 62.2-101.9 N) than all other repair types. Although the FDS slip reconstruction was not as strong as the intact state (82.1 N vs 156.2 N, respectively), it was 2.6 times stronger than the lateral band centralization (82.1 N vs 31.6 N, respectively) and 3 times stronger than a primary repair (82.1 N vs 27.6 N, respectively)., Conclusions: Reconstruction of the central slip using a distally-based FDS slip provided the greatest biomechanical strength compared with the direct repair or lateral band centralization., Clinical Relevance: The use of a distally based reconstruction using FDS may allow for safer early motion., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Increasingly more pregnant women are living with pre-existing multimorbidity (≥two long-term physical or mental health conditions). This may adversely affect maternal and offspring outcomes. This study aims to develop a core outcome set (COS) for maternal and offspring outcomes in pregnant women with pre-existing multimorbidity. It is intended for use in observational and interventional studies in all pregnancy settings., Methods and Analysis: We propose a four stage study design: (1) systematic literature search, (2) focus groups, (3) Delphi surveys and (4) consensus group meeting. The study will be conducted from June 2021 to August 2022. First, an initial list of outcomes will be identified through a systematic literature search of reported outcomes in studies of pregnant women with multimorbidity. We will search the Cochrane library, Medline, EMBASE and CINAHL. This will be supplemented with relevant outcomes from published COS for pregnancies and childbirth in general, and multimorbidity. Second, focus groups will be conducted among (1) women with lived experience of managing pre-existing multimorbidity in pregnancy (and/or their partners) and (2) their healthcare/social care professionals to identify outcomes important to them. Third, these initial lists of outcomes will be prioritised through a three-round online Delphi survey using predefined score criteria for consensus. Participants will be invited to suggest additional outcomes that were not included in the initial list. Finally, a consensus meeting using the nominal group technique will be held to agree on the final COS. The stakeholders will include (1) women (and/or their partners) with lived experience of managing multimorbidity in pregnancy, (2) healthcare/social care professionals involved in their care and (3) researchers in this field., Ethics and Dissemination: This study has been approved by the University of Birmingham's ethical review committee. The final COS will be disseminated through peer-reviewed publication and conferences and to all stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid Suprabio TM ) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.

Background: The impact of childhood atopic dermatitis (AD) on social and behavioral issues is not well understood., Objective: This study sought to determine the prevalence and predictors of social and behavioral symptoms and functional impairment among US children with AD., Methods: The 1996 to 2015 Medical Expenditure Panel Surveys were analyzed, including a representative, cross-sectional study of 2553 US children with AD. Behavioral and functional issues were examined using Columbia Impairment Scale (CIS) scores., Results: Childhood AD was associated with behavioral and functional problems, particularly nervousness (odds ratio [OR], 1.18; 95% confidence interval [95% CI], 1.06-1.31), home behavior (OR, 1.18; 95% CI, 1.06-1.32), staying out of trouble (OR, 1.18; 95% confidence interval, 1.06-1.31), and relationships with other kids (OR, 1.17; 95% CI, 1.05-1.31) and with siblings (OR, 1.14; 95% CI, 1.02-1.28). Higher CIS scores were present in children with AD versus without AD (adjusted β, 0.62; 95% CI, 0.22-1.02) and with psoriasis (adjusted β, 0.86; 95% CI, 0.22-1.49). Among children with AD, higher CIS scores were notably associated with male sex, older age, lower household income, public insurance, and comorbid depression and anxiety., Conclusions: AD was associated with behavioral and functional impairment, similar to psoriasis and other common chronic conditions. There are significant sociodemographic differences in CIS scores., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 American Contact Dermatitis Society. All Rights Reserved.)

Pyroelectricity plays a crucial role in modern sensors and energy conversion devices. However, obtaining materials with large and nearly constant pyroelectric coefficients over a wide temperature range for practical uses remains a formidable challenge. Attempting to discover a solution to this obstacle, we combined molecular design of labile electronic structure with the crystal engineering of the molecular orientation in lattice. This combination results in electronic pyroelectricity of purely molecular origin. Here, we report a polar crystal of an [FeCo] dinuclear complex exhibiting a peculiar pyroelectric behavior (a substantial sharp pyroelectric current peak and an unusual continuous pyroelectric current at higher temperatures) which is caused by a combination of Fe spin crossover (SCO) and electron transfer between the high-spin Fe ion and redox-active ligand, namely valence tautomerism (VT). As a result, temperature dependence of the pyroelectric behavior reported here is opposite from conventional ferroelectrics and originates from a transition between three distinct electronic structures. The obtained pyroelectric coefficient is comparable to that of polyvinylidene difluoride at room temperature., (© 2021. The Author(s).)

Introduction: Child mortality remains highest in regions of the world most affected by HIV/AIDS. The aim of this study was to assess child mortality rates in relation to maternal HIV status from 2005 to 2015, the period of rapid HIV treatment scale-up in Rwanda., Methods: We used data from the 2005, 2010 and 2015 Rwanda Demographic Health Surveys to derive under-2 mortality rates by survey year and mother's HIV status and to build a multivariable logistic regression model to establish the association of independent predictors of under-2 mortality stratified by mother's HIV status., Results: In total, 12 010 live births were reported by mothers in the study period. Our findings show a higher mortality among children born to mothers with HIV compared with HIV negative mothers in 2005 (216.9 vs 100.7 per 1000 live births) and a significant reduction in mortality for both groups in 2015 (72.0 and 42.4 per 1000 live births, respectively). In the pooled reduced multivariable model, the odds of child mortality was higher among children born to mothers with HIV, (adjusted OR, AOR 2.09; 95% CI 1.57 to 2.78). The odds of child mortality were reduced in 2010 (AOR 0.69; 95% CI 0.59 to 0.81) and 2015 (AOR 0.35; 95% CI 0.28 to 0.44) compared with 2005. Other independent predictors of under-2 mortality included living in smaller families of 1-2 members (AOR 5.25; 95% CI 3.59 to 7.68), being twin (AOR 4.93; 95% CI 3.51 to 6.92) and being offspring from mothers not using contraceptives at the time of the survey (AOR 1.6; 95% CI 1.38 to 1.99). Higher education of mothers (completed primary school: (AOR 0.74; 95% CI 0.64 to 0.87) and secondary or higher education: (AOR 0.53; 95% CI 0.38 to 0.74)) was also associated with reduced child mortality., Conclusions: This study shows an important decline in under-2 child mortality among children born to both mothers with and without HIV in Rwanda over a 10-year span., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 56-year-old woman with Down syndrome presented with right-sided weakness and dysarthria, and was found on CT/CTA to have a left middle cerebral artery infarct secondary to moyamoya disease. Her left posterior inferior cerebellar artery (PICA) was fed both by the left vertebral artery, and the left ascending pharyngeal artery (APA), with a variant origin from the internal carotid artery (ICA), then passing through the jugular foramen (Figure 1). Her right PICA originated exclusively from her right occipital artery, also via the jugular foramen (Figure 2). The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated from the brachiocephalic trunk. In addition, she had a trifurcated anterior cerebral artery (ACA), and just prior to this trifurcation, her left ACA was partially supplied by the left ICA, via a superior hypophyseal artery. This case is noteworthy for several reasons. First, though it is exceedingly rare to have the PICA supplied by the jugular branch of the APA, this is the first reported case with an ICA origin of that APA.1,2 The fact that both PICAs in this patient originate from the anterior circulation should remind clinicians that in unexplained posterior circulation infarctions, vascular anatomy should be explored, as carotid-vertebrobasilar anastomoses such as these are rare, but possible. Lastly, the conjunction of moyamoya disease and anomalies of the vertebrobasilar system in a patient with Down syndrome raises interesting questions about the influence of trisomy 21 on the developing vasculature. Connections from the APA to the vertebrobasilar system are hypothesized to result from a lack of regression of an embryological anastomosis, in line with the more common persistent trigeminal and persistent hypoglossal arteries.1 Patients with moyamoya disease have a significantly higher rate of persistent carotid-vertebrobasilar anastomoses than the general population,3 and are also 26 times more likely to have Down syndrome.4 Correspondingly, patients with Down syndrome have significantly higher levels of moyamoya disease, and are more than 10 times as likely as the general population to have abnormalities of the Circle of Willis5 and vertebral arteries.6 Several genes on chromosome 21 are known to affect angiogenesis, namely collagen XIII/endostatin (COL18A1), DYRK1A, and Down syndrome candidate region 1 (DSCR1), possibly through inhibition of VEGF activity.7 Whether additional copies of these genes are responsible for the anomalous vascular development seen in Down syndrome, in turn predisposing to the development of moyamoya disease, could benefit from further exploration.

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group ( n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBio TM ; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules ( n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

Objective: Eating self-efficacy behavior is an important predictor of successful lifestyle intervention. This secondary analysis evaluated the changes in eating self-efficacy behavior in patients with type 2 diabetes (T2D) and overweight/obesity following structured lifestyle intervention based on the Malaysian customized transcultural Diabetes Nutrition Algorithm (tDNA)., Methods: Patients with T2D and overweight/obesity (n = 230) were randomized either into the tDNA group which included a structured low-calorie meal plan using normal foods, incorporation of diabetes-specific meal replacements, and an exercise prescription or usual T2D care (UC) for 6 months. Patients in the tDNA group also received either counseling with motivational interviewing (tDNA-MI) or conventional counseling (tDNA-CC). The UC group received standard dietary and exercise advice using conventional counseling. Eating self-efficacy was assessed using a locally validated Weight Efficacy Lifestyle (WEL) questionnaire. All patients were followed up for additional 6 months' post-intervention., Results: There was a significant change in WEL scores with intervention over one-year [Group X Time effect: F = 51.4, df = (3.4, 318.7), p<0.001]. Compared to baseline, WEL scores improved in both the tDNA groups with significantly higher improvement in the tDNA-MI group compared to the tDNA-CC and UC groups at 6 months (tDNA-MI: 25.4±2.1 vs. tDNA-CC: 12.9±2.8 vs. UC: -6.9±1.9, p<0.001). At 12 months' follow-up, both the tDNA groups maintained improvement in the WEL scores, with significantly higher scores in the tDNA-MI group than tDNA-CC group, and the UC group had decreased WEL scores (tDNA-MI: 28.9±3.1 vs. tDNA-CC: 11.6±3.6 vs. UC: -13.2±2.1, p<0.001). Patients in the tDNA-MI group with greater weight loss and hemoglobin A1C reduction also had a higher eating self-efficacy, with a similar trend observed in comparative groups., Conclusion: Eating self-efficacy improved in patients with T2D and overweight/obesity who maintained their weight loss and glycemic control following a structured lifestyle intervention based on the Malaysian customized tDNA and the improvement was further enhanced with motivational interviewing., Clinical Trial: This randomized clinical trial was registered under National Medical Research Registry, Ministry of Health Malaysia with registration number: NMRR-14-1042-19455 and also under ClinicalTrials.gov with registration number: NCT03881540., Competing Interests: The authors of this manuscript declare that there is no conflict of interest or potential competing interest for this work.The diabetes-specific formula was provided by Abbott Nutrition, Malaysia, who also funded the study. This does not alter the adherence to PLOS ONE policies on sharing data and materials.

Despite advances in secondary prevention strategies in patients with cardiovascular disease, the residual risk of recurrent atherothrombotic events remains high. Dual-antiplatelet therapy is the standard of care for secondary prevention in patients with acute coronary syndrome (ACS), whereas single antiplatelet therapy, generally with aspirin, is the standard of care for secondary prevention in stable patients with coronary artery disease (CAD), peripheral artery disease (PAD), or cerebrovascular disease. However, atherosclerotic plaque disruption not only triggers platelet activation but also results in thrombin generation because of tissue factor exposure. Therefore, blocking both pathways by combining antiplatelet therapy with an anticoagulant, or dual pathway inhibition (DPI), has the potential to be more effective than inhibiting either pathway alone. The benefit of DPI has been demonstrated in the ATLAS ACS 2-TIMI 51, COMPASS, and VOYAGER PAD trials, where the combination of rivaroxaban vascular dose (2.5 mg twice daily) plus aspirin significantly reduced the risk of atherothrombotic events compared with aspirin across a broad range of patients, including those with recent ACS, those with chronic CAD and/or PAD, and patients with PAD who have undergone peripheral revascularization. This article provides the rationale for this regimen in more detail, including why the DPI regimen with the rivaroxaban vascular dose was developed for vascular protection in a broad spectrum of patients with atherosclerotic disease., Competing Interests: J.I.W. received honoraria from Anthos, Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Novartis, Pfizer, PhaseBio, Portola, Servier, and Tetherex Pharmaceuticals and institutional grants from Bayer AG and Boehringer Ingelheim. D.J.A. has received payment as an individual for: (a) consulting fee or honorarium from Amgen, Aralez Pharmaceuticals, AstraZeneca, Bayer AG, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Pfizer, PhaseBio, PLx Pharma, Sanofi, and The Medicines Company; (b) participation in review activities from CeloNova BioSciences and St. Jude Medical; (c) institutional payments for grants from Amgen, AstraZeneca, Bayer AG, Biosensors, CeloNova BioSciences, CSL Behring, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Idorsia Pharmaceuticals, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical RenalGuard Solutions, and the Scott R. MacKenzie Foundation. T.G. received grants and personal fees from Bayer AG, Bristol-Myers Squibb, Daiichi Sankyo, and The Medicines Company, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Ferrer, MSD, and Pfizer, grants from Siemens Healthcare and Spartan Bioscience outside the submitted work. S.H. is an employee of Bayer AG. D.J.A. reports grants and personal fees from Amgen, grants and personal fees from Aralez, grants and personal fees from Bayer, grants and personal fees from Biosensors, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Chiesi, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Eli Lilly, personal fees from Haemonetics, grants and personal fees from Janssen, grants and personal fees from Merck, personal fees from PhaseBio, personal fees from PLx Pharma, personal fees from Pfizer, grants and personal fees from Sanofi, personal fees from The Medicines company, grants and personal fees from CeloNova, personal fees from St Jude Medical, grants from CSL Behring, grants from Eisai, grants from Gilead, grants from Idorsia Pharmaceuticals Ltd, grants from Matsutani Chemical Industry Co., grants from Novartis, grants from Osprey Medical, grants from Renal Guard Solutions, grants from Scott R. MacKenzie Foundation, grants from NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064 and NIH/NHGRI U01 HG007269, grants and personal fees from Astra Zeneca, outside the submitted work. T.G. reports personal fees from Astra Zeneca, personal fees from Boehringer Ingelheim, personal fees from Pfizer, grants and personal fees from Bayer AG, grants and personal fees from Bristol Myers Squibb, grants and personal fees from Daiichi Sankyo, grants and personal fees from Eli Lilly, personal fees from Ferrer, outside the submitted work. J.I.W. reports personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from Daiichi-Sankyo, personal fees from Ionis, personal fees from Janssen, personal fees from Merck, personal fees from Novartis, personal fees from Pfizer, personal fees from Portola, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Laparoendoscopic transhiatal esophagectomy (THE) provides advantages over traditional THE by not only avoiding laparotomy but by also allowing more precise esophageal mobilization. Occasionally, the length of the gastric conduit is insufficient to allow delivery into the neck after laparoscopic mobilization and requires laparotomy to complete the procedure. We hypothesize that the need for laparotomy will correlate with the measurement of mediastinal height (distance from thoracic vertebrae T1-T12) on chest CT., Methods: Medical records of all patients who underwent attempted laparoendoscopic-assisted THE at a tertiary referral center between March 1, 2003 and January 31, 2019 were reviewed. Patients' mediastinal height was measured using computed tomography (CT) imaging of the chest by investigators and analyzed for correlation between mediastinal height and successful completion of a totally laparoendoscopic procedure., Results: A total of 21 cases met inclusion criteria: 9 successful laparoendoscopic THE procedures and 12 failed laparoendoscopic THE procedures (those requiring addition of a mini-laparotomy or thoracotomy). The mean mediastinal length for successful laparoendoscopic surgery was 23.5 cm, whereas the mean mediastinal length for failed laparoscopic surgeries was 24.8 cm (P = .03). Patient's overall height was not found to correlate with the need for conversion., Conclusions: Shorter mediastinal length is associated with successful laparoendoscopic or laparoscopic THE. This information is readily available to clinicians from routine preoperative staging studies (chest CT) and may be used to potentially predict the success rate of a totally laparoendoscopic approach and aid in patient selection. Further prospective evaluation of these findings is warranted.

With the assembly of increasing numbers of plant genomes, it is becoming accepted that a single reference assembly does not reflect the gene diversity of a species. The production of pangenomes, which reflect the structural variation and polymorphisms in genomes, enables in depth comparisons of variation within species or higher taxonomic groups. In this review, we discuss the current and emerging approaches for pangenome assembly, analysis and visualisation. In addition, we consider the potential of pangenomes for applied crop improvement, evolutionary and biodiversity studies. To fully exploit the value of pangenomes it is important to integrate broad information such as phenotypic, environmental, and expression data to gain insights into the role of variable regions within genomes., (Copyright © 2019. Published by Elsevier Ltd.)

While many regulators of axon regeneration have been identified, very little is known about mechanisms that allow dendrites to regenerate after injury. Using a Drosophila model of dendrite regeneration, we performed a candidate screen of receptor tyrosine kinases (RTKs) and found a requirement for RTK-like orphan receptor (Ror). We confirmed that Ror was required for regeneration in two different neuron types using RNA interference (RNAi) and mutants. Ror was not required for axon regeneration or normal dendrite development, suggesting a specific role in dendrite regeneration. Ror can act as a Wnt coreceptor with frizzleds (fzs) in other contexts, so we tested the involvement of Wnt signaling proteins in dendrite regeneration. We found that knockdown of fz, dishevelled (dsh), Axin, and gilgamesh (gish) also reduced dendrite regeneration. Moreover, Ror was required to position dsh and Axin in dendrites. We recently found that Wnt signaling proteins, including dsh and Axin, localize microtubule nucleation machinery in dendrites. We therefore hypothesized that Ror may act by regulating microtubule nucleation at baseline and during dendrite regeneration. Consistent with this hypothesis, localization of the core nucleation protein γTubulin was reduced in Ror RNAi neurons, and this effect was strongest during dendrite regeneration. In addition, dendrite regeneration was sensitive to partial reduction of γTubulin. We conclude that Ror promotes dendrite regeneration as part of a Wnt signaling pathway that regulates dendritic microtubule nucleation., Competing Interests: The authors have declared that no competing interests exist.

Background: Atopic dermatitis (AD) is associated with altered skin barrier, microbiome, and immune dysregulation that may increase risk of skin infections., Objective: The aim of the study was to determine whether AD is associated with skin infections and related outcomes., Methods: Data from the 2006 to 2012 National Emergency Department Sample were analyzed, including an approximately 20% sample of all US emergency department (ED) visits (N = 198,102,435 adults or children)., Results: Skin infections were increased in ED visits of adults (7.14% vs 3.76%) and children (5.15% vs 2.48%) with AD. In multivariable logistic regression models, AD was associated with significantly higher odds of skin infection in adults (adjusted odds ratio [95% confidence interval] = 1.93 [1.89-1.97]) and children (2.23 [2.16-2.31]). Pediatric and adult AD were associated with significantly higher odds of carbuncle/furuncles, impetigo, cellulitis, erysipelas, methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections, molluscum contagiosum, cutaneous warts, herpes simplex and zoster viruses, eczema herpeticum, dermatophytosis, and candidiasis of skin/nails and vulva/urogenitals. Adults with AD had significantly higher odds of genital warts (1.51 [1.36-1.52]) and herpes (1.23 [1.11-1.35]). Skin infections were associated with US $19 million excess annual costs of ED care in persons with AD., Conclusions: Atopic dermatitis patients had higher odds of multiple bacterial, viral, fungal, and sexually transmitted skin infections.

Confusion and conflict arise when infection prevention and control (IPC) policies lead to allegations of religious discrimination. Many IPC standards are generic in construct, often failing to address wider issues and general policy applicable to all may have unequal impact on minority groups. Achieving uniformity by treating everyone the same is not necessarily the same as treating them equally. Some variation in approach might be acceptable, often desirable and sometimes inevitable but must not compromise staff safety or patient welfare. Concerns regarding clinical safety may overlook or override cultural and religious; without care, the outcome might change from cooperative to confrontational. Where, and how, to draw the line?, Competing Interests: Declaration of conflicting interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Traditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy., Competing Interests: M.S. has received speaker fees from Abbott, Aspen, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, and Sanofi; travel grants from Bard, Bayer, Bristol-Myers Squibb, Medtronic, and Terumo; research grants from Cook, Daiichi Sankyo, and Terumo; and consulting fees from Bayer, Bristol-Myers Squibb, Daiichi Sankyo, and Sanofi. J.W. has received consultancy fees and honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, Portola, Anthos, and Tetherex., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: The incidence of malignant melanoma has been rising steadily over the past decades and Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a high mortality rate. Sentinel lymph node (SLN) biopsy is a recommended prognostic tool in primary cutaneous malignant melanomas of intermediate thickness and in all clinically node-negative Merkel cell carcinomas. The gold standard method for identification of SLNs is lymphoscintigraphy, which involves radioactive tracers. Indocyanine green-based near-infrared fluorescence imaging (NIRFI) has been also used for intraoperative SLN identification. We aim to evaluate the diagnostic sensitivity of the VisionSense VS3 NIRFI device for SNL identification. This device uses stereoscopic 3D high definition for both fluorescence and visible light imaging. Our hypothesis is that SLNs may be identified transcutaneously using fluorescent dye injections and NIRFI; therefore, obviating the need for lymphoscintigraphy in the future. METHODS AND ANALYSIS:: lymph node identification in skin malignancy using indocyanine green transcutaneously is a prospective diagnostic sensitivity study conducted at the Department of Plastic and Hand Surgery at the University Hospital Berne, Inselspital, Switzerland. The study aims at recruiting 93 patients (start date September 2017) to compare the accuracy of VisionSense VS3 camera at identifying SLNs transcutaneously with the current gold standard, lymphoscintigraphy. Moreover, a secondary objective is to determine if anatomical location of the SLN and patient factors (eg, body mass index, age) have an impact on the ability of VisionSense to detect SLNs when compared with the same gold standard., Trial Registration Number: ClinicalTrials.gov NCT03545334.

Background: Postpartum contraception is important for spacing and limiting childbirth. Although the use of modern contraception has been shown to reduce maternal and child morbidities and mortalities, postpartum women have one of the highest unmet needs for family planning. Inter-birth intervals less than 24 months have adverse effects on both the mother and the child, yet very limited empirical evidence exist on contraceptive use among postpartum women in Ghana. This study sought to determine the prevalence and determinants of modern contraceptive use among postpartum women in the Tema Metropolis, Ghana., Methods: A facility-based cross-sectional survey was conducted among 320 postpartum women with babies aged between three and 15 months. Participants were recruited from child welfare clinics in two government health facilities in the Tema metropolitan area using a simple random sampling technique. Data were analyzed using STATA version 15. Chi-square and multiple logistic regressions techniques were used to examine associations between postpartum contraceptive use and key independent variables. Statistical significance was set at p  = 0.05. Adjusted odds ratios and their 95% confidence intervals were used to assess the strength of association., Results: The prevalence rate of modern contraceptive use among postpartum women was 26.3%. Postpartum contraceptive use was significantly associated with past contraceptive use [AOR = 7.7 (95%CI: 3.4-17.5)]; return of menses [AOR = 4.3 (95%CI: 1.7-11.3)]; resumption of sexual activity [AOR = 4.7 (95%CI: 1.4-15.4)]; discussion of family planning with male partner [AOR = 3.1 (95%CI: 1.03-9.2)]; male partners' approval of modern contraception [AOR = 18.1 (95%CI: 6.3-51.6)]; family planning counselling received during antenatal care [AOR = 3.5 (95%CI: 1.3-9.9)] and knowledge of at least one modern methods of contraception available at the health facility [AOR = 4.7 (95%CI: 1.9-11.5)]., Conclusions: Postpartum contraceptive uptake is low among women in the Tema area. Factors that influence modern contraceptive uptake among postpartum women include past modern contraceptive use, resumption of sexual activity and menstruation, male partner involvement in contraception, family planning counselling during antenatal care and knowledge of the modern methods of contraception available at the health facility. Strengthening family planning education and counselling during antenatal care and using a multi-prong strategy to engage men as partners in family planning will improve postpartum contraceptive uptake., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Active communication between researchers and society is necessary for the scientific community's involvement in developing science-based policies. This need is recognized by governmental and funding agencies that compel scientists to increase their public engagement and disseminate research findings in an accessible fashion. Storytelling techniques can help convey science by engaging people's imagination and emotions. Yet, many researchers are uncertain about how to approach scientific storytelling, or feel they lack the tools to undertake it. Here we explore some of the techniques intrinsic to crafting scientific narratives, as well as the reasons why scientific storytelling may be an optimal way of communicating research to nonspecialists. We also point out current communication gaps between science and society, particularly in the context of neurodiverse audiences and those that include neurological and psychiatric patients. Present shortcomings may turn into areas of synergy with the potential to link neuroscience education, research, and advocacy., (Copyright © 2019 the authors.)

Androgens are known to be an essential regulator of male health. Androgen receptor (AR) is widely expressed throughout the adrenal cortex, yet the wider role for androgen signalling in the adrenal remains underexplored. To investigate AR-dependent and AR-independent androgen signalling in the adrenal, we used a novel mouse model with a specific ablation of androgen receptor in the adrenal cortex with or without reduction of circulating androgen levels by castration. Our results describe AR expression in the human and mouse adrenal and highlight that the mouse is a viable model to investigate androgen signalling in the adrenal cortex. We show androgen signalling via AR is required for X-zone regression during puberty. Furthermore, cortex measurements define differences in X-zone morphology depending on whether circulating androgens or AR have been removed. We show androgens promote both cortical cell differentiation and apoptosis but are dispensable for the formation of the definitive cortex. Additionally, investigation of aged mice with AR ablation reveals severe cortex disruption, spindle cell hyperplasia and X-zone expansion. The data described herein demonstrates AR-signalling is required to facilitate X-zone regression, cell clearance and to protect against adrenal degeneration during ageing.

Seizures are a feature not only of the many forms of epilepsy, but also of global metabolic diseases such as mitochondrial encephalomyopathy (ME) and glycolytic enzymopathy (GE). Modern anti-epileptic drugs (AEDs) are successful in many cases, but some patients are refractory to existing AEDs, which has led to a surge in interest in clinically managed dietary therapy such as the ketogenic diet (KD). This high-fat, low-carbohydrate diet causes a cellular switch from glycolysis to fatty acid oxidation and ketone body generation, with a wide array of downstream effects at the genetic, protein, and metabolite level that may mediate seizure protection. We have recently shown that a Drosophila model of human ME (ATP6 1 ) responds robustly to the KD; here, we have investigated the mechanistic importance of the major metabolic consequences of the KD in the context of this bioenergetics disease: ketogenesis, reduction of glycolysis, and anaplerosis. We have found that reduction of glycolysis does not confer seizure protection, but that dietary supplementation with ketone bodies or the anaplerotic lipid triheptanoin, which directly replenishes the citric acid cycle, can mimic the success of the ketogenic diet even in the presence of standard carbohydrate levels. We have also shown that the proper functioning of the citric acid cycle is crucial to the success of the KD in the context of ME. Furthermore, our data reveal that multiple seizure models, in addition to ATP6 1 , are treatable with the ketogenic diet. Importantly, one of these mutants is TPI sugarkill , which models human glycolytic enzymopathy, an incurable metabolic disorder with severe neurological consequences. Overall, these studies reveal widespread success of the KD in Drosophila, further cementing its status as an excellent model for studies of KD treatment and mechanism, and reveal key insights into the therapeutic potential of dietary therapy against neuronal hyperexcitability in epilepsy and metabolic disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The hypothalamic-pituitary-adrenal (HPA) axis regulates responses to internal and external stressors. Many patients diagnosed with conditions such as depression or anxiety also have hyperactivity of the HPA axis. Hyper-stimulation of the HPA axis results in sustained elevated levels of glucocorticoids which impair neuronal function and can ultimately result in a psychiatric disorder. Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised. To determine the role of glucocorticoid signalling in the hindbrain we have developed a novel mouse model that specifically ablates hindbrain GR to ascertain its role in behaviour, HPA-axis regulation and adrenal structure. Our study highlights that ablation of GR in the hindbrain results in excessive barbering, obsessive compulsive digging and lack of cage exploration. These mice also develop kyphosis, elevated circulating corticosterone and severe adrenal cortex disruption. Together, this data demonstrates a role for hindbrain GR signalling in regulating stress-related behaviour and identifies a novel mouse model to allow further investigation into the pathways impacting stress and anxiety.